Molecular Characteristics of Pediatric Patients With Sickle Cell Anemia and Stroke

Cerebrovascular accidents (CVA) are serious complications of sickle cell anemia (SS) in children. Factors that predispose children to this complication are not well established. In an effort to elucidate the risk factors associated with CVA in SS, we have determined the a-globin genotype and the bS haplotype of children with this complication. Among 700 children with SS followed at Children’s Hospital of Michigan, 41 (6%) are on chronic transfusions because of stroke due to cerebral infarction. The mean age of patients with CVA at the time of stroke was 5.6 ± 3.2 years (mean ± SD). The male/female ratio was 2/3. Only 8 of 41 patients (19.5%) had one a-gene deletion, compared to the reported preva-lence of 30 % in African-Americans. None of the patients had two a-gene deletions, and two (5%) had five a-genes. These findings are different than those in our adult patients with SS, where the prevalence of −a/−a and aaa/aa is 4 % and <2%, respectively. Ten different bS-haplotypes were detected in the patients studied. The majority of the patients (31%) were doubly heterozygous for the Ben/CAR haplotypes followed by Ben/Ben, Ben/ Sen, and CAR/CAR haplotypes, respectively. The prevalence of these haplotypes, with the exception of the CAR/CAR haplotype, was higher in females than males. All the patients with CAR/CAR haplotype were males, had four a-genes, and ranked third in prevalence. Three patients were heterozygous for the Cameron haplotype. The Cameron and atypical haplotypes were more prevalent than reported in patients with SS at large. The data suggest that CVA in children seems to occur more frequently in females and in patients with certain bS haplotype. a-Gene deletion seems to offer a protective effect against this complication. Neonates with four or more a-genes whose bS haplotype is Ben/CAR, atypical, or CAR/CAR seem to be at a higher risk for CAV than other patients. A prospective study on a larger group of patients with or without CVA may clarify thi